Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation
| Autor: | Hussein Hamzeh, René Pascal, U. Benjamin Kaupp, Heinz G. Körschen, Long Gui, Ansgar Poetsch, Luis Alvarez, Fedir Lavryk, Reinhard Seifert, Daniela Nicastro, Wolfgang Bönigk, Timo Strünker, Astrid Müller, Christian Trötschel, Andreas Rennhack |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Proteomics Electron Microscope Tomography cilium electron tomography Motility quantitative mass spectrometry Flagellum Article Mass Spectrometry General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Arbacia punctulata 0302 clinical medicine Animals Cilia Cyclic GMP Molecular Biology 030304 developmental biology Arbacia 0303 health sciences General Immunology and Microbiology Sperm flagellum biology Chemotaxis General Neuroscience Cilium Phosphodiesterase Articles biology.organism_classification Spermatozoa Sperm Cell biology fertilization Flagella Guanylate Cyclase Calcium signaling 030217 neurology & neurosurgery Neuroscience Signal Transduction |
| Zdroj: | The EMBO Journal EMBO Journal |
| ISSN: | 1460-2075 0261-4189 |
| Popis: | Cilia serve as cellular antennae that translate sensory information into physiological responses. In the sperm flagellum, a single chemoattractant molecule can trigger a Ca2+ rise that controls motility. The mechanisms underlying such ultra‐sensitivity are ill‐defined. Here, we determine by mass spectrometry the copy number of nineteen chemosensory signaling proteins in sperm flagella from the sea urchin Arbacia punctulata. Proteins are up to 1,000‐fold more abundant than the free cellular messengers cAMP, cGMP, H+, and Ca2+. Opto‐chemical techniques show that high protein concentrations kinetically compartmentalize the flagellum: Within milliseconds, cGMP is relayed from the receptor guanylate cyclase to a cGMP‐gated channel that serves as a perfect chemo‐electrical transducer. cGMP is rapidly hydrolyzed, possibly via “substrate channeling” from the channel to the phosphodiesterase PDE5. The channel/PDE5 tandem encodes cGMP turnover rates rather than concentrations. The rate‐detection mechanism allows continuous stimulus sampling over a wide dynamic range. The textbook notion of signal amplification—few enzyme molecules process many messenger molecules—does not hold for sperm flagella. Instead, high protein concentrations ascertain messenger detection. Similar mechanisms may occur in other small compartments like primary cilia or dendritic spines. Reversed enzyme‐messenger ratios in sperm cilia ensure high‐sensitivity, low noise messenger detection. |
| Databáze: | OpenAIRE |
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